The role of polymorphic cytochrome P450 gene(CYP2B6)in B-chronic lymphocytic leukemia(B-CLL)incidence and outcome among Egyptian patients

Cytochromes P450(CYPs)play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75%of the total metabolism of commercially available drugs,including chemotherapeutics.The gene expression and enzyme activity of CYPs are variable between individuals,which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics,as well as differences in the efficacy and toxicity of clinically used drugs.This research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients,as well as the clinical outcome after receiving cyclophosphamide chemotherapy.DNA was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex-and age-matched healthy individuals.The presence of the CYP2B6*9(G516T)polymorphism was examined by PCR-based allele specific amplification(ASA).Patients were further indicated for receiving chemotherapy,and then they were followed up.The CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models,comprising allelic(T-allele vs.G-allele,OR=4.8,p<0.001)and dominant(GT+TT vs.GG,OR=5.4,p<0.001)models.Following cyclophosphamide chemotherapy,we found that the patients with variant genotypes(GT+TT)were less likely to achieve remission compared to those with the wild-type genotype(GG),with a response percentage of(37.5%vs.83%,respectively).In conclusion,our findings showed that the CYP2B6*9(G516T)polymorphism is associated with B-CLL susceptibility among Egyptian patients.This variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.

Influence of Hemoglobin S Haplotypes on the Responses to Hydroxyurea Treatment in Children with Sickle Cell Disease in Abidjan, Côte d’Ivoire

Background: In Côte d’Ivoire so far, the circulating haplotypes have been inferred on the phenotypic profiling of SCD patients. The impact of the circulating haplotypes on the use of Hydroxyurea has not been assessed yet. Therefore the objective of this study is to identify in Abidjan the HbS haplotypes that modulate HU treatment responses. Methods: In a cross-sectional descriptive and analytical study, children aged 5 to 15 years with SCD, and carrying the hemoglobin phenotypes SSFA2 and SFA2, were recruited into a HU treatment cohort. Various parameters on the haplotypes and the outcomes of the treatment were analyzed. Results: Thirty nine children with SCD were included. The phenotypic profile of the cohort was 86.6% of SSFA2 and 15.4% of SFA2. Three haplotypes were found, the Benin haplotype, the Senegal haplotype, and an atypical one. The participants belonged to three genotypes, Benin/atypical (64.1%), Benin/Senegal (33.3%) and Senegal/Senegal (2.6%). Overall, HU treatment was successful in all haplotypes with 12 out of 39 patients failing treatment after 12 months in the Benin haplotype group. The association between HU treatment success and the Benin haplotype was found in terms of the decrease in the number of white blood cells and the students missing class. Conclusion: The study revealed that inferring haplotype based on the phenotypic profile could be inaccurate. The proportion of atypical haplotype that were not previously described in Côte d’Ivoire was high. All the haplotypes seemed to be associated with HU treatment success but some patients with Benin haplotype did not respond well.

Infection in Multiple Myeloma: Microbiological Profile and Prognosis in Senegalese Patients

Introduction: Infections are additional factors of morbidity and mortality in multiple myeloma (MM), and the current recommendation is antibiotic prophylaxis. In sub-Saharan Africa, few data on infectious complications of MM are available. We aim to describe the microbiological features of infections in MM, and their impact on survival in Senegalese patients. Methods: A retrospective (January 2005-January 2022), analytic, multicenter study on infections in patients followed for MM (IMWG criteria) in Senegalese clinical hematology services. The socio-epidemiological, diagnostic, microbiological, evolutionary and survival aspects were analyzed. Results: The study included 106 patients with multiple myeloma who had an infection at admission or during the treatment. Ten patients have the comorbidity (hypertension, lupus, type 2 diabetes). These patients had 136 infectious events identified at diagnosis (79.2%) or during chemotherapy (20.8%). The sites of infection are lung (42.6%), urinary (29.4%), dermatological (6.6%), digestive (5.2%), osteoarticular (4.4%), ear, nose and throat (3.7%), central nervous system (1.5%), or without site. We recorded 26.4% of patients with multi-site infections. The causal pathogens are bacteria (Gram-negative bacilli: 22.1%;Gram positive bacilli: 9.5%, Mycobacterium tuberculosis: 13.3%), parasitique (plasmodium falciparum 6.6%), viruses (SARS-COV2: 2.9%, VZV: 2.2%) and fungal (2.9%). Survival was reduced in patients who had an infection at the time of multiple myeloma diagnosis (p: 0.189) and those who had multiple infectious foci (p: 0.011). Conclusion: Infections in multiple myeloma are more frequent at diagnosis. The germs are varied and mostly bacteria, particularly gram-negative bacteria, and Kochs bacillus. Our study reveals that multiple infectious foci are a poor prognosis factor. It is necessary to evaluate the infectious risk early, and to adopt an antibiotic prophylaxis based on our tropical environment.

Involvement of haptoglobin in disease development

Haptoglobin(HP)is a liver glycoprotein that is actively synthesized during in-flammatory and hemolytic processes.It also has pro-oxidant and proinflam-matory properties,which are a function of its genotype.The genetic polymorp-hism of the chains leads to synthesis of three phenotypes/proteins,which are related to the number and type of chains and their molecular weight,namely HP1-1,HP1-2 and HP2-2.Patients with HP2-2 have more vascular complications,while those with HP1-1 have fewer.HP is involved in the worsening of diseases,such as HP2-2 in aggravation of vaso-occlusive crises in sickle cell disease,and worsening of the pathophysiology of other diseases.In contrast,HP1-1 confers better protection against diseases.All of this suggests that further studies should be conducted,including experimental and analytical studies focused on de-monstrating the influence of different HP genotypes on individual clinical and hematological data.This would help in understanding the role played by this genetic polymorphism in the pathophysiology of diseases.

Stem cell-based regenerative opportunities for the liver: State of the art and beyond

The existing mismatch between the great demand for liver transplants and the number of available donor organs highlights the urgent need for alternative therapeutic strategies in patients with acute or chronic liver failure. The rapidly growing knowledge on stem cell biology and the intrinsic repair processes of the liver has opened new avenues for using stem cells as a cell therapy platform in regenerative medicine for hepatic diseases. An impressive number of cell types have been investigated as sources of liver regeneration: adult and fetal liver hepatocytes,intrahepatic stem cell populations,annex stem cells,adult bone marrow-derived hematopoietic stem cells,endothelial progenitor cells,mesenchymal stromal cells,embryonic stem cells,and induced pluripotent stem cells. All these highly different cell types,used either as cell suspensions or,in combination with biomaterials as implantable liver tissue constructs,have generated great promise for liver regeneration. However,fundamental questions still need to be addressed and critical hurdles to be overcome before liver cell therapy emerges. In this review,we summarize the state-of-the-art in the field of stem cell-based therapies for the liver along with existing challenges and future perspectives towards a successful liver cell therapy that will ultimately deliver its demanding goals.

Interrogating the interplay of angiogenesis and immunity in metastatic colorectal cancer

Colon cancer is the third most common malignancy and the fifth most frequent cause of death from neoplastic disease worldwide.At the time of diagnosis,more than 20%of patients already have metastatic disease.In the last 20 years,the natural course of the disease has changed due to major changes in the management of metastatic disease such as the advent of novel surgical and local therapy approaches as well as the introduction of novel chemotherapy drugs and targeted agents such as anti-epidermal growth factor receptor,anti-BRAF and antiangiogenics.Angiogenesis is a complex biological process of new vessel formation from existing ones and is an integral component of tumor progression supporting cancer cells to grow,proliferate and metastasize.Many molecules are involved in this proangiogenic process,such as vascular endothelial growth factor and its receptors on endothelial cells.A well-standardized methodology that is applied to assess angiogenesis in the tumor microenvironment is microvascular density by using immunohistochemistry with antibodies against endothelial CD31,CD34 and CD105 antigens.Even smaller molecules,such as the micro-RNAs,which are small non-coding RNAs,are being studied for their usefulness as surrogate biomarkers of angiogenesis and prognosis.In this review,we will discuss recent advances regarding the investigation of angiogenesis,the crosstalk between elements of the immune microenvironment and angiogenesis and how a disorganized tumor vessel network affects the trafficking of CD8+T cells in the tumor bed.Furthermore,we will present recent data from clinical trials that combine antiangiogenic therapies with immune checkpoint inhibitors in colorectal cancer.

Influence of Haptoglobin and Hemoglobin Phenotypic Polymorphisms on Sickle Cell Disease Morbidity

Objectives: Sickle cell disease (SCD) has a varied clinical and biological expression depending on the hemoglobin phenotype: SSFA2, SFA2, SAFA2 and SC. Considering the antioxidant properties of the different haptoglobin phenotypes (Hp 1-1, Hp 2-1, Hp 2-2), it seemed relevant to know their influence on the morbidity of the different hemoglobin phenotype of SCD. Thus, the objective of this study was to identify associations between haptoglobin phenotype and morbidity of different SCD phenotypes. Methods: In a retrospective cross-sectional descriptive and analytical study, with a cohort of 170 black African carriers of hemoglobin S, in Ivory Coast, West Africa, hemoglobin and haptoglobin phenotypes were determined by electrophoretic methods. Results: The three major phenotypes of haptoglobin polymorphism were found in the SCD cohort: Hp 1-1 (24.1%), Hp 2-1 (56.5%), Hp 2-2 (19.4%). Vaso-occlusions were associated with haptoglobin phenotype Hp 1-1, (OR = 2.03;CI95% = [1.06 - 3.9];p Conclusions: Haptoglobin phenotype was associated to morbidity-adjusted hemoglobin phenotype. The study revealed a greater probability of a worse morbidity when the hemoglobin phenotype is homozygous. Unexpectedly, the worse morbidity is associated to Hp 1-1 haptoglobin phenotype, the most powerful antioxidant within the different haptoglobin phenotypes. Associations found were not systematic and need further studies to enlighten the determinism of SCD morbidity.

Baseline neutrophil-lymphocyte ratio and platelet-lymphocyte ratio appear predictive of immune treatment related toxicity in hepatocellular carcinoma

BACKGROUND A well-recognized class effect of immune checkpoint inhibitors(ICI)is immune-related adverse events(IrAEs)ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontinuation of ICI.Deaths are reported in<5%of patients treated with ICI.There are,however,no reliable markers to predict the onset and severity of IrAEs.We tested the association between neutrophil-lymphocyte ratio(NLR)and platelet-lymphocyte ratio(PLR)at baseline with development of clinically significant IrAEs(grade≥2)in hepatocellular carcinoma(HCC)patients treated with ICI.AIM To test the association between NLR and PLR at baseline with development of clinically significant IrAEs(grade≥2)in HCC patients treated with ICI.METHODS Data was extracted from an international database from a consortium of 11 tertiary-care referral centers.NLR=absolute neutrophil count/absolute lymphocyte count(ALC)and PLR=platelet count/ALC.Cutoff of 5 was used for NLR and 300 for PLR based on literature.We also tested the association between RESULTS Data was collected from 361 patients treated between 2016-2020 across the United States(67%),Asia(14%)and Europe(19%).Most patients received Nivolumab(n=255,71%).One hundred sixty-seven(46%)patients developed at least one IrAE,highest grade 1 in 80(48%),grade≥2 in 87(52%)patients.In a univariable regression model PLR>300 was significantly associated with a lower incidence of grade≥2 IrAEs(OR=0.40;P=0.044).Similarly,a trend was observed between NLR>5 and lower incidence of grade≥2 IrAEs(OR=0.58;P=0.097).Multivariate analyses confirmed PLR>300 as an independent predictive marker of grade≥2 IrAEs(OR=0.26;P=0.011),in addition to treatment with programmed cell death ligand 1(PD-1)/cytotoxic T lymphocyte-associated protein-4(OR=2.57;P=0.037)and PD-1/tyrosine kinase inhibitor(OR=3.39;P=0.01)combinations.Antibiotic use was not associated with IrAE incidence(OR=1.02;P=0.954).Patients treated with steroids had a>2-fold higher incidence of grade≥2 IrAEs(OR=2.74;P<0.001),although 74%were prescribed steroids for the treatment of IrAEs.CONCLUSION Given that high baseline NLR and PLR are associated with a decreased incidence of IrAEs,lower baseline NLR and PLR may be predictive biomarkers for the appearance of IrAEs in HCC treated with ICI.This finding is in keeping with several studies in solid tumors that have shown that baseline NLR and PLR appear predictive of IrAEs.

Etiology and portal vein thrombosis in Budd-Chiari syndrome

AIM: To research the etiology, portal vein thrombosis and other features of Budd-Chiari syndrome (BCS) patients prospectively. METHODS: A total of 75 patients (40 female, 35 male) who were diagnosed between January 2002 and July 2004 as having BCS were studied prospectively. Findings from on physical examination, ultrasonography, duplex ultrasonography and venography were analyzed. Hemogram and blood chemistry were studied at the time of diagnosis and on each hospital visit. Bone marrow examination and immune phenotyping were performed by a hematologist when necessary. Protein C, S, antithrombin Ⅲ, activated protein C resistance, and anticardiolipin antibodies, antinuclear antibodies, and anti ds-DNA were studied twice. The presence of ascite, esophageal varices, and portal thrombosis were evaluated at admission and on every visit. RESULTS: At least one etiological factor was determined in 54 (72%) of the patients. The etiology could not be defined in 21 (28%) patients. One etiological factor was found in 39, 2 factors in 14 and 3 factors in 1 patient. The most common cause was the web (16%), the second was Hydatid disease (11%), the third was Behcet’s disease (9%). Portal vein thrombosis was present in 11 patients and at least one etiology was identified in 9 of them (82%). CONCLUSION: Behcet’s disease and hydatid disease are more prominent etiological factors in Turkey than in other countries. Patients with web have an excellent response to treatment without signs of portal veinthrombosis while patients having thrombofilic factors more than one are prone to develop portal vein thrombosis with worse clinical outcome.

Targeted agents for second-line treatment of advanced hepatocellular carcinoma

Over the past ten years,sorafenib,a multikinase inhibitor,has been the standard of care for patients with unresectable hepatocellular carcinoma(HCC)and wellpreserved liver function.Recently,lenvatinib,a different multikinase inhibitor,was shown to be non-inferior to sorafenib,in terms of survival,while all other agents previously tested failed to prove non-inferiority(or superiority)when compared to sorafenib.Similarly,in the second-line setting,most investigational drugs failed to provide better survival outcomes than placebo.However,in the last 2 years three positive phase III trials have been published in this setting.The RESORCE trial,a phase III study evaluating regorafenib in HCC patients who experienced disease progression after first-line treatment with sorafenib,showed better outcomes with regorafenib compared to placebo.More recently,the phase III CELESTIAL trial demonstrated the superiority of cabozantinib,a multikinase inhibitor targeting vascular endothelial growth factor receptor,MET,and AXL,vs placebo in the second-and third-line setting in patients progressing on or intolerant to sorafenib.The survival benefits of a sustained anti-angiogenic inhibition were demonstrated also with ramucirumab in the phase III REACH-2 trial in patients previously treated with sorafenib and who had high baseline alpha-fetoprotein levels.Overall,the adverse events reported in these trials were in line with the known safety profiles of the tested agents.After nearly a decade of a certain degree of stagnation,we are now witnessing a period of novel therapeutic advances with multikinase inhibitors and monoclonal antibodies that will likely change the treatment scenario of HCC.

Aplastic anemia and severe pancytopenia during treatment with peg-interferon,ribavirin and telaprevir for chronic hepatitis C

Telaprevir and Boceprevir are the first direct acting antivirals approved for chronic hepatitis C in combination with peg-interferon alfa and ribavirin.Pancytopenia due to myelotoxicity caused by these drugs may occur,but severe hematological abnormalities or aplastic anemia(AA) have not been described.We collected all cases of severe pancytopenia observed during triple therapy with telaprevir in four Spanish centers since approval of the drug in 2011.Among 142 cirrhotic patients receiving treatment,7 cases of severe pancytopenia(5%) were identified and three were consistent with the diagnosis of AA.Mean age was 59 years,five patients had compensated cirrhosis and two patients had severe hepatitis C recurrence after liver transplantation.Severe pancytopenia was diagnosed a median of 10 wk after the initiation of therapy.Three patients had pre-treatment hematological abnormalities related to splenomegaly.In six patients,antiviral treatment was interrupted at the onset of hematological abnormalities.Two patients died due to septic complications and one patient due to acute alveolar hemorrhage.The remaining patients recovered.Severe pancytopenia and especially AA,are not rare during triple therapy with telaprevir in patients with advanced liver disease.Close monitoring is imperative in this setting to promptly detect serious hematological disorders and to prevent further complications.

Current trends in management of hepatitis B virus reactivation in the biologic therapy era

Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk ofHBV reactivation is heightened by the use monoclonalantibodies, such as rituximab (anti-CD20) and alemtuzumab (anti-CD52) that cause profound and longlasting immunosuppression. Emerging data indicatethat HBV reactivation could also develop following theuse of other biologic agents, such as tumor necrosis factor (TNF)-α inhibitors. When HBV reactivation is di-agnosed, it is mandatory to suspend biologic treatmentand start antiviral agents immediately. However, preemptive antiviral therapy prior to monoclonal antibodyadministration is crucial in preventing HBV reactivationand its clinical consequences. Several lines of evidencehave shown that risk of HBV reactivation is greatlyreduced by the identifi cation of high-risk patients andthe use of prophylactic antiviral therapy. In this article, we discuss current trends in the management of HBV reactivation in immunosuppressed patients receiving biologic therapy, such as rituximab, alemtuzumab and TNF-α antagonists.

Autoimmune gastritis presenting as iron deficiency anemia in childhood

AIM: To characterize clinical, laboratorial, and histological profile of pediatric autoimmune gastritis in the setting of unexplained iron deficiency anemia investigation.

Alpha-fetoprotein screening in patients with hepatitis C-induced cirrhosis who achieved a sustained virologic response in the direct-acting antiviral agents era

To the Editor:Hepatocellular carcinoma (HCC) is the most common primary livertumorandthethirdcauseofcancer-relateddeathsworldwide. HCC is the consequence of malignant transformation of hepatocytes and mainly occurs in patients with cirrhosis. Hepatitis C virus (HCV) chronic infection is a leading cause of end-stage liver diseaseandHCCintheWesterncountries[1].Theapprovalof direct-acting antiviral agents (DAAs) for the treatment of HCV has revolutionized the management of the disease, as no absolute contraindication to treatment exists and sustained virological response

Clinical features of AIDS patients with Hodgkin's lymphoma with isolated bone marrow involvement:report of 12 cases at a single institution

Objective： To study the main clinical and histopathological features of 12 patients with Hodgkin＇s lymphoma （HL） diagnosed primarily from bone marrow （BM） involvement. Methods： We included 12 acquired immunodeficiency syndrome （AIDS） patients with HL assisted in the F. J. Mufiiz Infectious Diseases Hospital since January 2002 to December 2013. The diagnosis of ilL with primary BM involvement in patients was confirmed by clinical, histopathological, and immunohistochemical findings. Results： All patients presented ＂B＂ symptoms and pancytopenia. All of them had stage IV neoplasm disease because of BM infiltration. The median of CD4＋ T-cell counts was 114 cells/μL, and mixed cellularity （MC） was the most frequent histopathological subtype of 92% cases. Conclusion： When other causes are excluded, BM biopsy should be performed in AIDS patients with ＂B＂ symptoms and pancytopenia to evaluate BM infiltration by atypical lymphocytes.

Tumor biopsy and patient enrollment in clinical trials for advanced hepatocellular carcinoma

Tumor biopsies may help to reliably distinguish hepatocellular carcinoma(HCC) from other tumors, mostly cholangiocarcinoma as well as to identify the patient populations who most benefit from target-driven HCC treatments, in order to improve the success rate of experimental therapies. Clarifying tumor biology may also lead to identify biomarkers with prognostic role and/or enabling to predict response or resistance to therapies. Recently, clinical trials have more efficiently included biomarker endpoints and increasingly collected tumor tissue from enrolled patients. Due to their frail status and sometimes fast-progressing disease, the performance status of patients with HCC progressing on first-line therapy can deteriorate quickly, preventing their enrollment in clinical trials. However, the challenge of identifying the proper patient at the proper time can be overcome by periodic inter-department meetings involving the key specialists taking care of HCC patients, and solid networks between research centers and referring institutions. An early planned biopsy would also facilitate timely inclusion of patients in biology-driven clinical trials. Ultimately, institution of multidisciplinary teams can optimize treatment choice, biopsy timing, and quick enrollment of patients in clinical trials, before their performance status deteriorates.

Anatomo-Clinical Case: Coexistence of Tuberculosis with Axillary Lymph Node Metastasis in Breast Carcinoma

Introduction: The coexistence of tuberculosis with axillary lymph node metastasis in breast carcinoma is uncommon. Observation: We report a case of a patient aged 59 years presenting a painless nodule in the right breast for one year. The scan and mammography revealed a long-axis node of 3 × 2 × 1 cm in the upper outer quadrant of the right breast ranked stage IV by the American College of Radiology (ACR), associated with a set of axillary lymph nodes and the largest one measuring 15 × 15 × 20 millimeters (mm). The breast biopsy helped diagnose a Scarff Bloom Richardson (SBR) grade II non-specific invasive carcinoma, modified by Ellis and Elston. A right mastectomy associated with a lymph node dissection was performed. We noticed a not well defined and whitish 5 mm tumor mass associated with 16 lymph nodes removed. The histological examination confirmed the diagnosis of SBR grade II non-specific invasive carcinoma with invasion of 7 lymph nodes (N+ = 7/16). In 3 metastatic lymph nodes, there were epithelioid and gigantocellular granulomas with full central necrosis. The Ziehl Neelsen staining had highlighted acid-fast bacilli. The tumor was oestrogen and progesteron receptor, without an overexpression of the oncoprotein human epidermal growth factor receptor 2 (HER2), which corresponds to a 0 score and the Ki 67 proliferation index assessed at 10%. The patient was given an anti-tuberculosis treatment combining Rifampicin (H), Isoniazid (I), Pyrazinamid (Z), Ethambutol (E) over 2 months and secondly a combination of Rifampicin and Isoniazid over 4 months (2RHZE/4 RH). The anti-tumor chemotherapy used a protocol combining 3 FAC60+ 3 Docetaxel (F = Fluorouracil&#174;A = Adriblastin&#174;, C = Cyclophosphamid). Conclusion: This coexistence is uncommon, of incidental discovery and necessitates a multidisciplinary care.

Spontaneous conception after autologous hematopoietic stem cell transplantation： a case report

Dear Editor, Allogeneic or autologous hematopoietic stem cell transplantation （HSCT） allows many patients with hematological malignancies to obtain prolonged survival and often disease cure. Autologous HSCT is particularly effective in acute promyelocytic leukemia （APL）, a subtype of acute myeloid leukemia （AML） after relapse with conventional treatment. However, iatrogenic endocrine disturbances and reproductive failure are frequently-encountered late effects, which have a major impact on the quality oflife.l Conditioning regimens with total body irradiation （TBI） and intensive chemotherapy before autologons or allogeneic HSCT are known to cause permanent infertility, a risk that can be prevented by sperm banking.2

Pediatric palliative care- The role of the patient's family

Whenever a child suffers, what does she or he cry? Mother! What does that mean? Palliative care is not a type of medicine based on objective evidence or statistics. The only relevant standard is the very individual quality of life. Nobody knows better what this actually means but the patient himself. Thus, if the mother's presence has the biggest impact on a child's wellbeing or comfort, she herself is the most valuable treatment modality. In nearly every publication dealing with pediatric palliative care, it is stated that palliative care does not only imply care for the sick child but also for the parents and the whole family. Usually, it is pointed out that they are suffering a lot as well. But helping them does also mean: helping the child! Of course, it means higher efforts, obligations and costs for the healthcare system. Thus the justification of this effort may be put in question; in particular, it may be argued that disorders of family members should, if necessary, be treated as such. But this is only one side of the coin! In the following, we will, based on published literature, look at the role of mothers, fathers, and siblings for the wellbeing of an ill or even dying child. As a conclusion, we will learn that if it is our task to give a dying child the best available care, helping mothers, fathers and sibling is an inevitable part of it.

Down Protein C and S Antigen Could Be Predictor of Mortality Outcome in Critical Egyptian COVID-19 Illness

Background: One of the most serious morbidity and mortality features in COVID-19 is thrombo-embolic manifestation with disturbed hemostasis in natural anticoagulant. Protein S plays a critical role in cytokine storming and acts as cross talk between immune status and coagulation process. So, we aimed to address its role in addition to protein C in severity and outcome of disease, with its role in vaccinated people by AstraZeneca. Methods: The present study was conducted on 70 COVID-19 positive by real-time PCR. 40 of patients had moderate symptoms of respiratory, 30 cases were admitted into ICU of Mansoura University Hospital, some of them under mechanical ventilator. In addition to 40 healthy volunteers after first dose of vaccinated AstraZenka as reference, assessment of protein C&S antigen was done by ELIZA. Results: Significant increase in total leucocytic count in COVID-19 than vaccinated volunteer with significant reduction in absolute lymphocytosis, increased neutrophilia. First significant observation was higher MPV in COVID-19 than vaccinated, in addition to significantly higher C-reactive protein in severe cases than moderate and vaccinated. Prominent interesting finding in our study was significant reduction in Protein C&S in severe cases than moderate and vaccinated. Logistic regression analysis revealed that both could be predictor of mortality outcome as CRP in COVID-19 illness. Conclusion: There was significant reduction in protein C&S in severe cases than moderate and vaccinated. Regression analysis shows that could be predictor of mortality as well as CRP, D-dimer. Large extended study and follow up are needed to assess the incidence of thromboembolism and role of protein C&S in different variety protocols of vaccination programs.